1. Field of the Invention
This invention relates to a container for cell culture production, and, more particularly, to a roller bottle having at least one angled exterior pleat for achieving a high cell growth surface area on the interior of the bottle and for facilitating access to all surface areas by liquids deposited in the bottle.
2. Description of the Related Art
One type of container commonly used in laboratories for culturing cells is know as a “roller bottle”. Roller bottles are generally cylindrical and are adapted to rotate about their vertical axes. The internal surfaces of such roller bottles provide active regions for culturing cells. A liquid growth medium is introduced into the roller bottle. The rotating movement of the bottle keeps the internal surfaces wetted with the liquid medium, thereby encouraging the growth of cells.
Rotating rollers of an appropriate apparatus rotate these roller bottles. It is desirable to grow large amounts of cells, mostly for cell by-products, such as pharmaceutical substances that are secreted by cells. Various approaches have been used to increase the internal surface area of roller bottles. One approach has been to increase the amount of actual surface area available for cell growth.
Some roller bottles are produced unitarily by a blow-molding technique and include longitudinal pleats in the walls of the roller bottle. The longitudinal pleats increase the effective internal surface area of the roller bottle, and extend into the growth chamber for increasing culture or cell yield.
It is further known to provide a culture vessel having such longitudinal pleats, and further including circumferential collars that encircle the external surface of the top and bottom ends of the vessel. The collars maximize the vessel's grip point when the vessel is placed on its side on the rollers of a rotating apparatus such as a roller rack.
The prior art also discloses a roller bottle having pleats perpendicular to the longitudinal axis of the bottle for increasing the surface area for growing cells and further including at least one unpleated longitudinal drain panel. Reinforcing ribs on the exterior of the bottle parallel to the longitudinal axis of the bottle extend along the outer edge of the cross-wise corrugation for strengthening the pleated bottle.
It is also known to use circumferential ribs on a roller bottle for reinforcing the bottle walls. In this regard, the prior art discloses a roller bottle having flexible plastic walls and a plurality of spaced-apart circumferential reinforcement rings defined in the flexible plastic walls to cause the body to retain a generally cylindrical shape.
A problem associated with prior art roller bottles, especially those having pleats for expanding the surface area for growing cells, has been the tendency of the bottle walls to expand when the insides of the bottles become pressurized. This expansion causes the bottle to stop rolling on a roller rack. The absence of rotation causes portions of the surfaces to become dry and promotes cell death in these dry areas.
Another problem associated with prior art roller bottles relates to the ability to assure that liquid placed in the roller bottle will achieve maximum contact with all interior surface regions of the pleated walls. In this regard, it has been determined that roller bottles with circumferential pleats will distribute liquid efficiently within any given pleat as the roller bottle is rotated about its axis. However, liquid may not be distributed uniformly among the various circumferential pleats. Although longitudinal pleats allow liquid to flow longitudinally along the grooves defined by the pleats, rotation of such a longitudinal-pleated roller bottle about its longitudinal axis does not always distribute liquid efficiently from one longitudinal pleat to another, and also results in increased agitation of the liquid, which is detrimental to cell growth and cultivation.
It is desirable therefore to provide a pleated roller bottle which safeguards against bottle expansion under pressure to thereby allow the roller bottle to continue rolling on a roller rack.
It is also desirable to provide roller bottles with a pleat arrangement that permits efficient flow of liquid to all surface areas defined by the pleats while maintaining agitation of the liquid.